(Official February 1,2006)

A:Infrared Absorption á197Kñ—

B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.

Buffer solution,Mobile phase,Standard stock solution 1,Standard stock solution 2,and Chromatographic system— Proceed as directed in theAssay.

Standard solution— Use theStandard preparation,prepared as directed in theAssay.

Test solution— Use theAssay preparation,prepared as directed in theAssay.

Procedure— Inject a volume (about 40µL)of theStandard solution and theTest solution into the chromatograph,record the chromatograms,and measure the peak areas.Calculate the percentages of phenytoin,phenytoin related compound A,phenytoin related compound B,and unknown impurities in each mLof Injection taken by the formula: in whichCis the concentration,in mg per mL,of the respective impurity in theStandard solution;Vis the volume,in mL,of the Injection taken to prepare theTest solution;Lis the labeled amount,in mg per mL,of fosphenytoin sodium in the Injection;andriandrSare the individual peak responses of the impurities in the chromatograms obtained from theTest solution and theStandard solution,respectively:not more than 1.5%of phenytoin related compound Bis found;not more than 0.2%of phenytoin is found;not more than 0.2%of phenytoin related compound Ais found;not more than 0.1%of any individual unknown impurity is found;and not more than 2.0%total impurities is found.[NOTE—Use the peak area and concentration of the USP Phenytoin RSin theStandard solution asrSandC,respectively,to calculate the percentage of the unknown impurities.]

Buffer solution— Dissolve about 8.2g of monobasic potassium phosphate in 1Lof water.Adjust with 6Npotassium hydroxide solution to a pHof 6.5±0.05.

Mobile phase— Prepare a filtered and degassed mixture ofBuffer solution,methanol,and acetonitrile (73:25:2).Make adjustments if necessary (seeSystem Suitability underChromatography á621ñ).

Standard stock solution 1— Dissolve an accurately weighed quantity of USP Fosphenytoin Sodium RSin methanol,and dilute quantitatively,and stepwise if necessary,withBuffer solution to obtain a solution having a known concentration of about 0.75mg per mL.

Standard stock solution 2— Dissolve an accurately weighed quantity of USP Phenytoin RS,USP Phenytoin Related Compound A RS,and USP Phenytoin Related Compound B RSin methanol,and dilute quantitatively,and stepwise if necessary,with methanol to obtain a solution having a known concentration of about 0.0075mg per mL,0.0075mg per mL,and 0.015mg per mL,respectively.

Standard preparation— Transfer 10.0mLofStandard stock solution 1and 5.0mLofStandard stock solution 2to a 50-mLvolumetric flask.Dilute withBuffer solution to volume,and mix.

Assay preparation— Transfer an accurately measured volume of the Injection,equivalent to about 300mg of fosphenytoin,to a 200-mLvolumetric flask,dilute with methanol to volume,and mix.Transfer 5.0mLof this solution to a 50-mLvolumetric flask.Dilute withBuffer solution to volume,and mix.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 214-nm detector and a 4.6-mm ×15-cm column that contains packing L11.The flow rate is about 1.25mLper minute.Chromatograph theStandard preparation,and record the peak responses as directed forProcedure:the relative retention times are about 0.3for phenytoin related compound B,about 0.5for phenytoin related compound A,1.0for fosphenytoin,and about 3.8for phenytoin;the resolution,R,between phenytoin related compound Band phenytoin related compound Ais not less than 4.0;the column efficiency is not less than 2250theoretical plates for the fosphenytoin peak;the tailing factor is not more than 1.8for the fosphenytoin peak;and the relative standard deviation for replicate injections is not more than 1.0%for the fosphenytoin peak and not more than 5.0%for the phenytoin related compound B,phenytoin related compound A,and phenytoin peaks.

Procedure— Separately inject equal volumes (about 40µL)of theStandard preparation and theAssay preparation into the chromatograph,record the chromatograms,and measure the peak areas for fosphenytoin.Calculate the quantity,in mg,of fosphenytoin sodium (C16H13N2Na2O6P)in each mLof the Injection taken by the formula: in whichCis the concentration,in mg per mL,of USP Fosphenytoin Sodium RSin theStandard preparation;Vis the volume,in mL,of the Injection taken to prepare theAssay preparation;andrUandrSare the fosphenytoin peak areas obtained from theAssay preparation and theStandard preparation,respectively.